Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism
The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumo...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | Arabian Journal of Chemistry |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222002982 |
| _version_ | 1818253385518809088 |
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| author | Zizhen Zhao Chen Fu Yuping Zhang Yingying Zhang Xiaoxi Yang Ailing Fu |
| author_facet | Zizhen Zhao Chen Fu Yuping Zhang Yingying Zhang Xiaoxi Yang Ailing Fu |
| author_sort | Zizhen Zhao |
| collection | DOAJ |
| description | The incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo. The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy. |
| first_indexed | 2024-12-12T16:39:14Z |
| format | Article |
| id | doaj.art-9a59d46ce7524ab79aad814a56efa91f |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-12-12T16:39:14Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-9a59d46ce7524ab79aad814a56efa91f2022-12-22T00:18:37ZengElsevierArabian Journal of Chemistry1878-53522022-08-01158103982Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanismZizhen Zhao0Chen Fu1Yuping Zhang2Yingying Zhang3Xiaoxi Yang4Ailing Fu5College of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaCollege of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaCorresponding author.; College of Pharmaceutical Science, Southwest University, Chongqing 400715, ChinaThe incidence of HCC continues to increase rapidly in recent years. the principle of developing anti-HCC drugs is to specifically kill tumor cells, without affecting the function of normal cells. Here we synthesized a novel protonic compound bis(5-amino-1,10-phenanthroline) (P-BAP), and the antitumor activity was explored in vitro and in vivo. The results showed that P-BAP could selectively inhibit the proliferation of tumor cells, and induce HCC apoptosis. In HCC-bearing mice, P-BAP could effectively retard the tumor growth, even completely eliminate the tumors at the dose of 5 mg/kg, and meanwhile P-BAP had no significant effect on mouse body weight. Mechanism analysis revealed that P-BAP could down-regulate the protein expressions of pleomorphic adenoma gene like-2 (PLAGL2), HIF-1α and β-catenin, and up-regulate the levels of pro-apoptotic protein BAX and BNIP3. In addition, P-BAP could reduce mitochondrial respiratory chain complex activities, leading to insufficient ATP production. The study provides a new approach for designing selective antitumor drugs, and suggests that P-BAP would be a potential candidate for HCC therapy.http://www.sciencedirect.com/science/article/pii/S1878535222002982Hepatocellular carcinomaProtonic bis-phenanthrolinePLAGL2ApoptosisHydrogen bond |
| spellingShingle | Zizhen Zhao Chen Fu Yuping Zhang Yingying Zhang Xiaoxi Yang Ailing Fu Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism Arabian Journal of Chemistry Hepatocellular carcinoma Protonic bis-phenanthroline PLAGL2 Apoptosis Hydrogen bond |
| title | Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism |
| title_full | Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism |
| title_fullStr | Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism |
| title_full_unstemmed | Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism |
| title_short | Inhibitory effect of protonic bis(5-amino-1,10-phenanthroline) on proliferation of hepatocellular carcinoma and its molecular mechanism |
| title_sort | inhibitory effect of protonic bis 5 amino 1 10 phenanthroline on proliferation of hepatocellular carcinoma and its molecular mechanism |
| topic | Hepatocellular carcinoma Protonic bis-phenanthroline PLAGL2 Apoptosis Hydrogen bond |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222002982 |
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